The present invention relates to methods and apparatus to control charge neutralization reactions between positive ions and negative ions in ion traps used for mass spectrometry.
Ion trap mass spectrometers, also known as quadrupole ion storage devices or Paul ion traps, use various combinations of RF and DC electric potentials applied to endcaps and ring electrodes which give rise to RF and DC electric fields that trap and manipulate ions. Various electric potentials are known including RF and DC quadrupolar and dipolar potentials. Electrospray ionization (ESI) and other ionization methods can produce multiply-charged analyte ions from large molecules including peptides and proteins and others. This permits certain analysis of high mass molecules by a mass spectrometer having a lower mass-to-charge range. It is also known to introduce counter ions of opposite charge, including singly-charged counter ions, which will react by ion/ion charge transfer reactions, including proton transfer reactions, to migrate the analyte ions to lesser multiple charged states which represent higher mass-to-charge ratios. However, it has been difficult to control the ion to ion transfer reactions so as to manipulate and/or control the ion/ion reactions for practical use in mass spectrometry.
One known method to selectively inhibit rates of ion/ion reactions in a quadrupole ion trap is to apply dipolar RF signals to the endcap electrodes to cause resonance excitation at or near the ion of interest. All of the higher charge state ions can undergo rapid ion/ion reactions until such time as they fall into the region of the Mathieu stability diagram where they become xe2x80x9cparkedxe2x80x9d by virtue of the reduced ion/ion reaction rates for the accelerated charge state. This method is described by Scott A. McLuckey Gavin E. Reid and J. Mitchell Wells, in xe2x80x9cIon Parking During Ion/Ion Reactions In Electrodynamic Ion Trapsxe2x80x9d, Analytical Chemistry, Vol. 74, Issue 2, pages 336-346, published Jan. 15, 2002.
The present invention includes new methods and apparatus to control charge neutralization reactions between positive ions and negative ions which are simultaneously trapped in a Paul type ion trap. The ion/ion reactions can be inhibited and/or suspended so as to allow further processing and/or analysis of the ion products. This is particularly useful for concentrating analyte ions in a particular charge state for subsequent processing such as purification, collision induced dissociation (CID), and mass analysis. Such concentration is particularly useful for the analysis of mixtures of high mass molecules such as proteins.
It is an object of the present invention to provide new methods and apparatus for operating an ion trap to control the progression of the ion/ion charge transfer reactions between simultaneously-trapped positive and negative ions to facilitate further processing and mass analysis.
It is another object of the present invention to provide methods and apparatus for generating and using combinations of dipolar DC and dipolar RF signals across endcap electrodes in a manner to manipulate and control ion/ion reactions in an ion trap containing positive and negative ions.
It is a further object of the present invention to provide methods and apparatus to apply dipolar DC and dipolar RF potentials to induce suspension and force resumption of charge state neutralization reactions and to quench further reactions in a manner controllable by an operator so as to select one or more target charge states for further processing and mass analysis.